The majority of cancer-related deaths result from recurrent or metastatic disease. The ability to detect tumor regions in a state of growth dormancy may aid in prediction of cell populations capable of these phenomenona, and thus help to guide treatment selection to effect complete response to therapy. The current inability to detect cancer dormancy represents an important deficiency in current conventional cancer imaging techniques, which traditionally rely on signatures of rapidly dividing and replicating cells, including lesion size and vascularity, to isolate regions of tumor viability. Hepatocellular Carcinoma (HCC) is the fastest growing cause of cancer death in the United States and provides a prime example of this deficiency. The most commonly used therapy to treat patients with HCC is transarterial embolization or transarterial chemoembolization (TA(C)E), a procedure performed by interventional radiologists that targets tumors by obstructing arterial blood flow into a tumor region with (TACE) or without the administration of intra-arterial chemotherapy (TAE). While traditional markers of tumor viability are absent after this intervention, recurrence is common. Prior research has demonstrated that recurrence in HCC following TA(C)E is made possible by the persistence of dormant cell populations in a nutrient- deprived environment. The ability to detect dormant cell populations in cancer following treatment is an unmet need in the management of HCC. The long-term goal is to prevent recurrence following TAE in HCC by supplemental pharmacologic or surgical treatment when dormant populations persist. The overall objective of this proposal is to develop a metabolic molecular imaging platform using hyperpolarized magnetic resonance imaging that can detect dormant populations in HCC on the basis of changes in metabolic pathway flux. The rationale is based on the fact that cells in a state of dormancy have alterations in metabolic gene expression and protein activity that result in changes in flux through metabolic pathways that can be detected non-invasively with appropriately selected imaging probes. The central hypothesis is that dormant cancer cells will have decreased anabolic metabolism and increased catabolic metabolism, which can be detected with hyperpolarized isotopes of metabolites in related pathways. This objective and central hypothesis will be pursued by the following specific aims: 1) identify differences in metabolic pathway flux in vitro for HCC cells in dormant and proliferative states to guide selection of hyperpolarized imaging probes, 2) validate the capacity of hyperpolarized probes to distinguish dormant and proliferative phenotypes of HCC in vitro, and 3) validate the capacity of hyperpolarized probes to detect cancer dormancy in a HCC rat model following TAE. The successful achievement of the proposed aims will have an immediate impact on clinical care by addressing a clinical deficiency in the care of patients with HCC. Moreover, the proposed paradigm holds implications for metabolic imaging of cancer cell heterogeneity with relevance beyond the detection of cancer dormancy.